Peripartum management of a parturient with Klippel‐Trénaunay syndrome

Summary

Klippel‐Trénaunay syndrome is a rare congenital disorder affecting the vascular and lymphatic systems. The clinical presentation can vary widely, but the syndrome is broadly characterised by capillary, venous and lymphatic malformations as well as limb hypertrophy. We present the case of a 35‐year‐old parturient who underwent an emergency caesarean section for suspected fetal distress, and describe the anaesthetic management during the peripartum period. Only a small number of similar cases have been described, and the multisystem nature of the condition presents several challenges to both the obstetric and anaesthetic management. The major points of concern to the anaesthetist are haematological, with a tendency to both abnormal bleeding and clotting disorders, compounded by vascular malformations which may present anywhere in the body including the epidural space and airway. Other considerations relate to limb hypertrophy and spinal abnormalities, as well as pulmonary and ocular sequelae and chronic pain. Strategies for safe patient management include early multidisciplinary involvement, and assessment of the presence and extent of any vascular anomalies with advanced imaging techniques. The risk of significant blood loss can be mitigated with antifibrinolytic and uterotonic medication as well as cell salvage, with treatment carefully balanced against the concurrent risk of thrombosis.

Introduction

Klippel‐Trénaunay syndrome is an eponymous syndrome named after French doctors Maurice Klippel and Paul Trénaunay, who first described the classical triad of capillary malformations, venous varicosities and limb hypertrophy in 1900 [1]. It is a complex but rare condition, with an estimated incidence of between 1:30,000 and 1:100,000 live births [2], although milder presentations may be under‐reported. Prevalence is consistent between ethnicities and it appears to be more common in men than women (1.5:1) [3].

The essential characteristics of Klippel‐Trénaunay syndrome were more recently defined as capillary and venous malformations with or without lymphatic malformation and limb overgrowth [4]. Vascular malformations can present anywhere in the body, including the abdomen, pelvis, airway and epidural space. Complications can include deep vein thrombosis, clotting disorders including disseminated intravascular coagulopathy, chronic venous insufficiency, cellulitis and pain. Furthermore, disease presentation varies widely and other features may include kyphoscoliosis, gait abnormalities and hyperhidrosis.

Recently Klippel‐Trénaunay syndrome has been attributed to sporadic congenital mutation of the phosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit alpha gene involved in regulation of angiogenesis, leading to angiodysplasia and over‐formation of both the affected vascular network and bone matrix [5]. Because somatic gene mutations identified are not present in germ cells, it is recognised as a non‐hereditary disease [2, 6]. Klippel‐Trénaunay syndrome is a clinical diagnosis, supported by imaging modalities such as duplex ultrasound and magnetic resonance angiography. The severity of the syndrome varies significantly and routine management is largely focused on symptom control, prevention and treatment of vascular sequalae.

Historically, case reports have indicated that pregnancy is contra‐indicated in Klippel‐Trénaunay syndrome due to increased risk of peripartum complications [2, 3]. In this report, we present a case of emergency caesarean section with successful outcome and discuss the anaesthetic and peri‐operative considerations associated with Klippel‐Trénaunay syndrome and the peripartum period.

Report

A 29‐year‐old gravida 2, para 1 woman in the 37^th week of pregnancy underwent elective induction of labour for essential hypertension without evidence of pre‐eclampsia or intra‐uterine growth restriction. She had been diagnosed with Klippel‐Trénaunay syndrome in infancy, and her other past medical history included hypertension, chronic back pain and deep vein thrombosis. She had undergone an uncomplicated general anaesthetic as a teenager for sclerotherapy of leg varicosities.

Her obstetric history comprised an uncomplicated vaginal delivery of her first child with no medical input. Magnetic resonance imaging of the spine performed during her first pregnancy demonstrated occult spinal dysraphism and tethering of the spinal cord with the conus medullaris terminating at L4. No vascular malformations were noted.

During her second pregnancy she was booked at a district general hospital but transferred to our tertiary centre in her third trimester. However, she was not reviewed in anaesthetic clinic and no further investigations were undertaken. Her medications included oral labetalol and prophylactic dose dalteparin, which had been withheld on admission to hospital 3 days previously. Her analgesic plan for labour comprised solely of entonox.

Induction of labour with prostaglandin was successful, however after a short time the cardiotocograph displayed pathological features and a category 1 caesarean section was indicated. An urgent anaesthetic review was requested at this point. Examination revealed hypertrophy of the left arm and leg with cutaneous capillary malformations, which were also noted to have spread to her abdomen and chest during pregnancy. Her body mass index was 36 kg.m^‐2 and airway assessment demonstrated Mallampati grade 3 with micrognathia. Her blood pressure was 149/104 mmHg; admission blood tests showed haemoglobin 144 g.l^‐1 and platelet count 189 × 10⁹.l^‐1.

Two 16‐G venous cannulae were inserted in the patient’s right arm and two units of packed red blood cells were cross‐matched. Informed consent for surgery and general anaesthesia were obtained; the patient was already aware that neuraxial anaesthesia was contra‐indicated.

Pre‐oxygenation was performed using high‐flow nasal oxygen at 30 litres per min, with particular care taken of positioning owing to the patient’s scoliosis and limb hypertrophy. Rapid sequence induction of general anaesthesia was performed with i.v. propofol 2 mg.kg^‐1 and rocuronium 1 mg.kg^‐1. A partial view of the glottis was obtained with a McGrath videolaryngoscope with a size 4 MAC blade (Medtronic, Watford, UK). Tracheal intubation over a gum‐elastic bougie was successful on the first attempt. General anaesthesia was maintained using sevoflurane 1.8% in a 50:50 mix of oxygen:nitrous oxide.

No vascular abnormalities were noted by the surgical or anaesthetic teams, and the neonate was delivered in good condition. Oxytocin 5 IU and tranexamic acid 1 g were given i.v. following delivery, and an oxytocin infusion was commenced. Fentanyl 100 µg, morphine 10 mg, paracetamol 1 g and compound sodium lactate 1 l were administered i.v.

The estimated blood loss was 700 ml, and 30 ml levobupivacaine 0.25% was infiltrated around the incision; neuromuscular blockade was antagonised with sugammadex 200 mg i.v. Tracheal extubation was uneventful and the patient was comfortable in the early postoperative period.

Postoperative analgesia was provided with regular paracetamol and morphine by patient‐controlled analgesia pump. Labetalol was continued postoperatively and a 6‐week course of prophylactic dalteparin was prescribed. The patient and her baby were discharged 2 days later.

Discussion

Due to its rarity and inconsistent clinical presentation, there has been some debate surrounding the defining characteristics of Klippel‐Trénaunay syndrome, with previous attempts to grade or classify the condition overlapping with symptoms with other diseases [7]. Our patient’s historic clinic letters stated a diagnosis of ‘Klippel‐Trénaunay‐Weber Syndrome’, previously used to describe a spectrum of Klippel‐Trénaunay syndrome with arteriovenous (AV) fistulae; however, this is now considered a clinically distinct entity known as Parkes Weber Syndrome [8]. Furthermore, our patient had no radiological evidence of AV malformations on ultrasound Doppler studies or magnetic resonance imaging.

Our patient had not undergone genetic counselling; the genetic alterations identified are not universal to the Klippel‐Trénaunay syndrome phenotype and as such do not form part of current diagnostic criteria [9]. In 2018, a formal definition was put forward by the International Society for the Study of Vascular Abnormalities to include capillary and venous malformations with or without lymphatic malformation and limb overgrowth [4].

Our patient had significant vascular and subcutaneous anomalies which predominantly affected her lower limbs, although she described them spreading across her abdomen and chest wall during pregnancy. These can be found anywhere on the body in patients with Klippel‐Trénaunay syndrome, and local overgrowth can range from superficial pigmentation to invasive lesions affecting underlying bones and soft tissue [8]. Whilst our patient reported chronic back pain, she did not regularly take analgesia for this which negated the need for antenatal rationalisation of pain medications or planning for complex postoperative pain management.

The clinical severity of lesions varies significantly and routine management is largely focused on symptom control and treatment of vascular sequalae. Venous anomalies may be treated with laser, sclerotherapy or ligation, and lymphatic malformations may respond to compression therapy, radiofrequency ablation or surgical resection [7]. Our patient had received sclerotherapy in her teenage years and had previously been counselled for varicose vein stripping which had not been undertaken.

Whilst our patient had undergone several antenatal investigations during her first pregnancy, she would ideally have been reviewed again in our obstetric anaesthesia clinic to assess her symptoms and peripartum risk. Case series suggest that the physiological changes associated with pregnancy exacerbate the risks of thromboembolism and major haemorrhage associated with Klippel‐Trénaunay syndrome, placing patients at higher risk [2, 6]. Of note, vascular malformations in the lower abdomen, pelvis and genitourinary system may require prenatal monitoring; we propose that repeat magnetic resonance imaging would have been indicated in our patient. This may have influenced both the mode of delivery chosen and requirement for interventional radiology, vascular, colorectal or gynaecological involvement [3].

Due to the rarity of the disease, there is a relative paucity of literature regarding obstetric anaesthetic risk and peripartum management of patients with Klippel‐Trénaunay syndrome. Associated morbidity and mortality are largely haematological, ranging from thromboembolic disease and venous hypertension leading to high‐output cardiac failure, to consumptive coagulopathy and haemorrhagic complications [10].

Although our patient had been diagnosed with essential hypertension before her pregnancy, there is no well‐described correlation between this and Klippel‐Trénaunay syndrome. However, pulmonary hypertension has been previously observed in case reports of similar patients, possibly secondary to either chronic thromboembolism or microvascular anomalies [9]. Pre‐eclampsia has not been observed at an increased rate in Klippel‐Trénaunay syndrome, although case numbers may be too small to draw firm conclusions [2]. Our patient was not taking aspirin during her pregnancy despite her hypertension, and although the reason for this is not documented, it may be owing to concerns about increased bleeding risk.

The principal clinical challenges identified during the case included the urgency of delivery, risk of significant intra‐operative blood loss from bleeding diathesis and undiagnosed pelvic vascular malformations, and potentially difficult airway management, which was of particular concern as neuraxial anaesthesia was contra‐indicated. Anticipation of these risks allowed us to take steps to minimise their potential impact, such as the elective use of video‐laryngoscopy, inserting two large‐bore venous cannulae, and commencing a uterotonic infusion to prevent atony. However, due to the short time between the patient arriving on labour ward and the decision for category 1 caesarean section, there was limited time for assessment and optimisation and cell salvage was unfortunately unavailable at short notice.

Perhaps the most significant concern for the obstetric anaesthetist is the risk of unrecognised vascular malformations within the spinal canal or epidural space; however, multiple case studies describing neuraxial techniques around known lesions have been described [2, 3]. Regional anaesthesia was already contra‐indicated in our patient due to concurrent spinal cord dysraphism, so further imaging of the spine would not have helped in this case. Other complications associated with Klippel‐Trénaunay syndrome and their anaesthetic implications are summarised in Table 1.

Table 1.

Complications associated with Klippel‐Trénaunay syndrome and peripartum anaesthetic considerations.

Associated complications	Anaesthetic considerations
Haemorrhagic complications
Thrombocytopaenia Chronic anaemia Increased risk of spontaneous bleeding including retroperitoneal and CVA, especially if concurrent AVMs	May have antibodies from previous blood transfusions, ensure cross‐matched blood available Haematinic investigations and pre‐delivery haemoglobin optimisation Low threshold for advanced imaging techniques if symptomatic Avoidance of ergometrine—increase arterial blood pressure can lead to increased risk of CVAs
Coagulopathies
Associated thrombophilia Risk of venous thrombosis and embolic events (DVT/PE) Consumptive coagulopathy (Kasabach‐Merritt syndrome) Disseminated intravascular coagulation Abnormal fibrinolysis	May be on prenatal anticoagulation or anti‐platelet agents or IVC filter in situ DIC may occur after even minor episodes of bleeding Consideration for point‐of‐care testing and peripartum antifibrinolytic agents Early administration of clotting factors, cryoprecipitate or fibrinogen concentrate Use of cell salvage if operative management required
Venous malformations
‘Port‐wine stain’ skin lesions Varicose veins Chronic venous insufficiency Superficial thrombophlebitis Blood pooling and risk of thrombosis Vascular malformations Difficult i.v. access	Postpartum VTE prophylaxis MRI angio scan to detect angiodysplastic structures near to the spinal cord, pelvis +/‐ lower abdominal wall—may require repeat scanning/monitoring if concerns regarding uterine involvement Paraspinal anomalies may exclude regional anaesthetic techniques Early placement of wide‐bore i.v. access, consideration of invasive monitoring
Hypertrophy of bones and soft tissues
Limb deformity Impaired mobility Chronic pain Spine: risk of scoliosis	Prenatal counselling and chronic pain team involvement, regional techniques and increased analgesic requirements Psychological and physiotherapy input Spinal ultrasound may help neuraxial blockade if not contra‐indicated
Lymphatic system abnormalities
Lymphoedema Lymphatic cysts (e.g. splenic) Cellulitis	Elastic compression stockings and pneumatic compression devices (also help prevent DVT formation and cellulitis) High risk of skin infections and bacteraemia may require perinatal antibiotic therapy
Pulmonary changes
Pulmonary hypertension Venous varicosities: pulmonary cavernous haemangiomas	Risk of spontaneous haemothorax – high vigilance for occult blood loss and signs of respiratory distress, haemoptysis Consider antenatal echocardiography
Other systems
Ocular: cataracts, retinal haemorrhage, glaucoma	Good peri‐operative eye care if general anaesthesia used including ointment and coverage

CVA, cerebrovascular accident; AVM, arteriovenous malformation; DVT, deep vein thrombosis; PE, pulmonary embolism; VTE, venous thrombo‐embolism.

Despite predictable haematological complications, we were fortunate that our patient had a high starting haemoglobin level and a relatively limited intra‐operative blood loss, and therefore did not require blood transfusion. She recovered well from the general anaesthetic; postoperative analgesic requirements were minimal; the patient was mobilising early and was discharged 2 days later. She received a prolonged course of prophylactic dalteparin, compression stockings and advised to be vigilant for signs of venous thrombo‐embolism.

Counselling patients regarding obstetric risk is challenging and should be addressed on an individual basis. Whilst treatment of Klippel‐Trénaunay syndrome is usually conservative unless specific complications occur, regular clinical and radiographic monitoring is crucial in order to assess the impact of pregnancy on disease progression [8].

Communication had a significant impact on our patient’s care and we believe that her transfer between hospitals resulted in limited antenatal investigation and risk stratification. For example, obstetric assessment regarding vulvo‐vaginal varicosities and subsequent bleeding risk may have altered the recommended delivery modality [2], or may have dictated the location and timing of induction of labour in a multiparous woman. We also believe that antenatal screening for hereditary and acquired thrombophilia should have been undertaken. Furthermore the risks associated with her condition, such as the possibility of spinal cord trauma associated with lithotomy positioning due to underlying spinal cord dysraphism, could have been better communicated.

Klippel‐Trénaunay syndrome encompasses a myriad of systemic anomalies that can have a significant impact on patients’ vascular and haematological systems. The rarity of the disease, variable phenotype expression and limited number of obstetric cases mean that there are no specific clinical guidelines or protocols to guide peripartum management. However case reports, including our own experience, demonstrate successful outcomes with meticulous peri‐operative care and multidisciplinary management.